Comparison of Chronocort® With Standard Glucocorticoid Therapy in Patients With Congenital Adrenal Hyperplasia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02716818|
Recruitment Status : Completed
First Posted : March 23, 2016
Last Update Posted : September 6, 2018
|Condition or disease||Intervention/treatment||Phase|
|Congenital Adrenal Hyperplasia||Drug: Chronocort® Drug: standard glucocorticoid therapy||Phase 3|
At baseline, subjects will be admitted overnight for a 24-hour endocrine profile whilst on their standard therapy. Subjects will attend the study site in the morning and have 17-hydroxyprogesterone (17-OHP) and androstenedione (A4) levels assessed at 15:00, 17:00, 19:00, 21:00, 23:00, 01:00, 03:00, 05:00, 07:00, 09:00, 11:00, 13:00 and 15:00. Safety laboratory tests, a DEXA scan for body composition, and height, weight and waist circumference will be recorded. Subjects will then be randomised to Chronocort® or to continue on their standard care. Randomisation will be stratified by baseline treatment:
- hydrocortisone only or
- prednisone or prednisolone, alone or in combination with hydrocortisone
- dexamethasone only or in combination with any other glucorticoid
The initial dose setting at the start of the Chronocort® treatment will be based on hydrocortisone dose equivalent of baseline therapy in accordance with standard clinical practice. Further dose refinement/titration will be conducted in both treatment groups as necessary after 4 weeks and 12 weeks using a standardised titration algorithm after the subject has been re-admitted for further 24-hour endocrine profiles. Safety endpoints will also be measured at the 07:00 morning sample of each 24-hour profile assessment day. The decision to change doses in both treatment groups will be made by a central independent blinded physician, with the actual change in dose then being made by the local investigator looking after the subject. At 6 months, all the baseline tests will be repeated (including the 24-hour profile). All subjects may then continue on Chronocort®, whatever their randomised treatment, as part of an open-label extension study (to be conducted under a separate protocol). Stress doses of hydrocortisone will be given throughout the study for intercurrent illnesses as medically indicated according to "sick day rules".
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||122 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase III Study of Efficacy, Safety and Tolerability of Chronocort® Compared With Standard Glucocorticoid Replacement Therapy in the Treatment of Congenital Adrenal Hyperplasia|
|Actual Study Start Date :||February 22, 2016|
|Actual Primary Completion Date :||July 28, 2018|
|Actual Study Completion Date :||July 28, 2018|
Chronocort® will be provided as 5mg, 10mg and 20mg capsules for oral administration. The starting dose for each subject will be based on the subjects previous glucocorticoid therapy dose and then dose titrated to effect.
Chronocort® is a patented oral modified release formulation of hydrocortisone which is intended to mimic, or closely match, the serum levels of endogenous cortisol.
Other Name: Hydrocortisone
Active Comparator: standard glucocorticoid therapy
Subjects in this arm will continue previous oral glucocorticoid therapy titrated to effect.
Drug: standard glucocorticoid therapy
Subjects in this arm will continue on their standard hydrocortisone therapy
- Change from baseline in 17-OHP [ Time Frame: 24 weeks ]Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) profile for 17-OHP.
- Change from baseline in A4 [ Time Frame: 24 weeks ]Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) profile for A4.
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 24 weeks ]AEs will be collected for all subjects from the time of consent up to 30 days ± 3 days following the last visit or, if applicable, the Early Withdrawal visit. Any ongoing AEs post study will be followed to resolution or stabilisation if resolution is not expected. Only treatment emergent AEs will be included in the main safety analysis: other AEs will be listed.
- Use and reasons for use of rescue medication [ Time Frame: 24 weeks ]The number of times the patients needed rescue medication (supplied as a 'sick day safety pack' plus instructions for use that are called the 'sick days rules') during the study wil be recorded. The reason for the use of the rescue medication will also be recorded.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02716818
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892-1932|
|Principal Investigator:||Debbie Merke, MD||National Institutes of Health (NIH)|